SOM230 Graves Orbitopathy pilot trial.|
|- candidate number||14264|
|- NTR Number||NTR3819|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||25-jan-2013|
|- Secondary IDs|| |
|- Public Title||SOM230 Graves Orbitopathy pilot trial.|
|- Scientific Title||SOM230 Graves Orbitopathy pilot trial.|
|- hypothesis||In this protocol we hypothesize that treatment of patients with moderate to severe Graves Orbitopathy with SOM230 when corticosteroids are contraindicated or unwanted, is beneficial.|
|- Healt Condition(s) or Problem(s) studied||Graves' orbitopathy|
|- Inclusion criteria||1. Moderate – severe GO;|
2. Corticosteroids contraindicated due to diabetes mellitus, severe osteoporosis, heart failure, psychosis, infectious diseases or other clinical relevant comorbidities;
3. Corticosteroids refused by patients;
4. Age > 18.
|- Exclusion criteria||1. Inability/refusal to give informed consent;|
3. GO (dysthyroid optical neuropathy) necessitating high dose steroids or acute decompression;
4. Abnormal thyroid function (defined as TSH >4.0 mU/l or FT4 <10 or >21 pmol/l);
6. Drug abuse and smoking.
|- mec approval received||no|
|- multicenter trial||no|
|- Type||Single arm|
|- planned startdate ||1-apr-2013|
|- planned closingdate||1-apr-2014|
|- Target number of participants||12|
|- Interventions||After screening and inclusion, patients will be treated with SOM230 long acting (intramuscular, 60 mgr once monthly) during 12 weeks (i.e. three dosages).|
|- Primary outcome||A validated overall ophthalmic/endocrine assessment at the CTEC with predefined criteria for success, no change and worsening of GO at 0, 4, 8 and 12 weeks.|
|- Secondary outcome||Quality of life (Qol) assessed by the GO-QoL, a validated disease-specific quality-of-life questionnaire to be completed by the patient at 0, 4, 8 and 12 weeks.|
|- Timepoints||Monthly during 12 weeks (i.e. three dosages).|
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES||MD. M.R. Soeters|
|- CONTACT for SCIENTIFIC QUERIES||MD. M.R. Soeters|
|- Sponsor/Initiator ||Academic Medical Center (AMC, Amsterdam)|
(Source(s) of Monetary or Material Support)
|Academic Medical Center (AMC)|
|- Publications||Optimal management of Graves orbitopathy: a multidisciplinary approach. Soeters MR, van Zeijl CJJ, Boelen A, Kloos R, Saeed P, Vriesendorp TM, et al. The Netherlands journal of medicine. 69(7):302–8.|
Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves' orbitopathy. Bartalena L, Krassas GE, Wiersinga W, Marcocci C, Salvi M, Daumerie C, Bournaud C, Stahl M, Sassi L, Veronesi G, Azzolini C, Boboridis KG, Mourits MP, Soeters MR, Baldeschi L, Nardi M, Currò N, Boschi A, Bernard M, von Arx G; European Group on Graves' Orbitopathy. J Clin Endocrinol Metab. 2012 Dec;97(12):4454-63.
|- Brief summary||Graves’ ophthalmopathy (GO), or Graves Orbitopathy, is clinically present in ~25% of patients with Graves’ disease (hyperthyroidism). There is consensus that patients with active, moderate-to-severe GO qualify for immunosuppression: weekly pulses of intravenous methylprednisolone for 12 weeks are recommended. However, because of disappointing response rates to prednisolone, alternative treatments with similar efficacy but less side effects would be welcome, not only in patients in whom steroids are contraindicated.
A number of studies, have demonstrated that octreotide and lanreotide do not improve or marginally improve eye changes as compared to placebo despite the fact the orbital fibroblast expresses the somatostatin receptor. The cause of these disappointing results could well be the low affinity of octreotide and lanreotide for all somatostatin receptors except subtype sst2, whereas in GO a clear up regulation of sst1 and sst5 on OF has been observed.
Pasireotide (SOM230) indeed has a greater inhibitory effect on in vitro proliferation of orbital fibroblasts than octreotide, and both pasireotide and octreotide inhibit human lymphocyte proliferation albeit acting at different concentrations.|
Result of a recent trial that we have performed showed disappointing results when moderate to severe GO patients were treated with intravenous prednisolone with improvement of a predefined response criterium in only ~50% of cases. Previous studies showed higher response rates, which may have been due to the fact that in these early studies patients with more severe GO were included. However, the response to intravenous prednisolone underscores the need of additional therapies.
Therefore, we aim to investigate in a pilot trial the effect of SOM230 on predefined endpoints in patients with moderate to severe GO whom have contraindications for prednisolone therapy or decline from prednisolone therapy for other reasons.
|- Main changes (audit trail)|
|- RECORD||25-jan-2013 - 4-feb-2013|
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